AMPHASTAR PHARMACEUTICALS, INC., INTERNATIONAL

AMPHASTAR PHARMACEUTICALS, INC., INTERNATIONAL
MEDICATION SYSTEMS, LTD., ACTAVIS, INC., AND
ACTAVIS PHARMACEUTICALS, INC.,
Petitioners,
V.
MOMENTA PHARMACEUTICALS, INC. AND SANDOZ, INC.
ON PETITION FOR A WRIT OF CERTIORARI
TO THE UNITED STATES COURT OF APPEALS
FOR THE FEDERAL CIRCUIT
PETITION FOR A WRIT OF CERTIORARI
Pratik A. Shah
Counsel of Record
Anthony T. Pierce
James E. Tysse
Hyland Hunt
Emily C. Johnson
AKIN GUMP STRAUSS
HAUER ~ FELD LLP
1333 New Hampshire
Ave., N.W.
Washington, D.C. 20036
(202) 887-4000
[email protected]
Counsel for Petitioners
WILSON-EPES PRINTING Co., INC. - (202) 789-0096 - WASHINGTON, D. C. 20002
BLANK PAGE
QUESTION PRESENTED
The Hatch-Waxman Act safe harbor provides
that "[i]t shall not be an act of infringement to ***
use *** a patented invention *** solely for uses
reasonably related to the development and
submission of information under a Federal law which
regulates the manufacture, use, or sale of drugs[.]"
35 U.S.C. § 271(e)(1). The question presented is:
Whether the safe harbor protects a generic drug
manufacturer’s bioequivalence testing that is
performed only as a condition of maintaining FDA
approval and is documented in records that must be
submitted to the FDA upon request.
6)
ii
PARTIES TO THE PROCEEDINGS
Petitioners Amphastar Pharmaceuticals, Inc.,
International Medication Systems, Actavis, Inc., and
Actavis Pharmaceuticals, Inc. were defendants in the
district court and appellees in the court of appeals.
Actavis Pharmaceuticals, Inc. was formerly known as
Watson Pharma, Inc.
Momenta Pharmaceuticals, Inc. and Sandoz,
Inc. were plaintiffs in the district court and
appellants in the court of appeals.
RULE 29.6 DISCLOSURE
Amphastar Pharmaceuticals, Inc.. has no parent
corporation, and no publicly held corporation owns
ten percent or more of its stock. International
Medication Systems, Ltd. is a wholly owned
subsidiary of Amphastar Pharmaceuticals, Inc.
Actavis, Inc. is a subsidiary of Actavis Capital S.a.r.l.,
a wholly owned subsidiary of Allergan plc. Actavis
Pharmaceuticals, Inc. is a wholly owned subsidiary of
Allergan plc. Teva Pharmaceuticals has announced a
deal to purchase Actavis Generics froIn Allergan plc,
but the deal has not closed.
ooo
111
TABLE OF CONTENTS
QUESTION PRESENTED ...........................................i
PARTIES TO THE PROCEEDINGS ..........................
RULE 29.6 DISCLOSURE .......................................... ii
TABLE OF AUTHORITIES ........................................v
OPINIONS BELOW .................................................... 1
JURISDICTION ..........................................................1
AND
STATUTORY
RE LEVANT
REGULATORY PROVISIONS ..............................2
INTRODUCTION ........................................................ 2
STATEMENT OF THE CASE ....................................4
4
A. Statutory and Regulatory Framework .............
B. Factual Background .........................................5
C. Procedural History ..........................................10
REASONS FOR GRANTING THE WRIT ................14
I. THE FEDERAL CIRCUIT’S CATEGORICAL
EXCLUSION OF "ROUTINE" USES FROM
THE HATCH-WAXMAN SAFE HARBOR
CONFLICTS WITH THIS COURT’S
15
PRECEDENTS AND THE STATUTE ................
A. Limiting The Safe Harbor’s Scope Based
On A General Purpose Divined From
Legislative History Conflicts With Eli
Lilly And Merck .............................................. 15
1. This Court’s precedents establish that
the safe harbor cannot be narrowed
15
by reference to legislative history ...........
iv
2. The Federal Circuit has engrafted an
atextual limitation on the safe harbor
in conflict with this Court’s cases ............
17
B. The Federal Circuit Erred In Excluding
From The Safe Harbor Testing Required
For Ongoing FDA Approval ............................
21
II. WHETHER HATCH-WAXMAN PROTECTS
TESTING REQUIRED FOR CONTINUED
FDA APPROVAL IS AN EXCEPTIONALLY
IMPORTANT QUESTION ................................... 24
CONCLUSION .......................................................... 27
APPENDIX
Opinion of the U.S. Court of Appeals for the
Federal Circuit (Nov. 10, 2015) .............................
la
Memorandum Opinion and Order of the U.S.
District Court for the District of
Massachusetts Granting Defendants’ Motion
for Summary Judgment (July 19, 2013) .............
39a
Opinion of the U.S. Court of Appeals for the
Federal Circuit Vacating Preliminary
Injunction (Aug. 3, 2012) ......................................56a
Memorandum Opinion and Order of the U.S.
District Court for the District of
Massachusetts Granting Plaintiffs’ Motion
for Preliminary Injunction (Oct. 28, 2011) .......
129a
Order of the U.S. Court of Appeals for the
Federal Circuit Denying Rehearing En Banc
(Feb. 17, 2016) ................................................... 162a
Final Judgment of the U.S. District Court for
the District of Massachusetts (Jan. 24, 2014).. 164a
35 U.S.C. § 271(e)(1) .......................................... 166a
V
TABLE OF AUTHORITIES
CASES:
Abtox Inc. v. Exitro Corp.,
122 F.3d 1019 (Fed. Cir. 1997) ............................12
Aventis Pharma S.A. v. Amphastar Pharms.,
Inc.,
525 F.3d 1334 (Fed. Cir. 2008) .............................. 6
Classen Immunotherapies, Inc. v. Biogen IDEC,
659 F.3d 1057 (Fed. Cir. 2011) .......... 13, 18, 19, 20
Eli Lilly & Co. v. Medtronic, Inc.,
496 U.S. 661 (1990) ...................................... passim
Integra Lifesciences I, Ltd. v. Merck KGaA,
331 F.3d 860 (Fed. Cir. 2003) ........................ 16, 19
Merck KGaA v. Integra Lifesciences I, Ltd.,
545 U.S. 193 (2005) ......................................passim
Morales v. Trans World Airlines, Inc.,
504 U.S. 374 (1992) ..............................................20
Pittston Coal Group v. Sebben,
488 U.S. 105 (1988) ..............................................18
PLIVA, Inc. v. Mensing,
131 S. Ct. 2567 (2011) ............................................4
Shannon v. United States,
512 U.S. 573 (1994) ..............................................18
vi
STATUTES AND REGULATIONS:
21 U.S.C.
§ 321(j) .................................................................... 8
§ 331(a) ................................................................... 8
§ 351(b) ............................................................... 2, 8
§ 355(a) ................................................................... 5
§ 355(j)(2)(A) ...........................................................4
§ 374(a)(4)(A) ..........................................................S
28 U.S.C.
§ 1254(1) ................................................................. 2
35 U.S.C.
§ 271(e)(1) ..................................................... passim
§ 271(g) ...................................................................9
Drug Price Competition and Patent Term
Restoration Act, Pub. L. No. 98-417, 98 Stat.
1585 (1984) .............................................................4
Federal Food, Drug, and Cosmetic Act, 21
U.S.C. § 301 et seq ................................................... 5
21 C.F.R.
§ 211.165(a) .............................................................8
§ 211.165(d) .............................................................8
§ 211.165(f) .............................................................8
§ 211.180(c) .............................................................8
§ 211.194(a)(1) ........................................................8
§ 211.194(a)(2) ........................................................8
OTHER AUTHORITIES:
H.R. REP. NO. 98-857(I) (1984), as reprinted in
1984 U.S.C.C.A.N. 2647 .......................................13
vii
H.R. REP. NO. 98-857(II) (1984), as reprinted in
1984 U.S.C.C.A.N. 2686 ................................. 23, 26
Meininger, D., IP Policy Forum: The Increasing
Importance of Biologics-Based Drugs in
Pharmaceutical Pipelines, 18 MAR@ INTELL.
PROP. L. REV. 19 (2014) ........................................25
Morrow, Thomas & Linda Hull Felcone,
Defining the Difference: What Makes
Biologics Unique ...................................................25
7
USP General Notices and Requirements ...................
USP Guideline for Submitting Requests for
Revision to USP-NF: General Information
10
for All Submissions (Apr. 2016) ...........................
BLANK PAGE
No. 15AMPHASTAR PHARMACEUTICALS, INC., INTERNATIONAL
MEDICATION SYSTEMS, LTD., ACTAVIS, INC., AND
ACTAVIS PHARMACEUTICALS, INC.,
Petitioners,
Vo
MOMENTA PHARMACEUTICALS, INC. AND SANDOZ, INC.
ON PETITION FOR A WRIT OF CERTIORARI
TO THE UNITED STATES COURT OF APPEALS
FOR THE FEDERAL CIRCUIT
PETITION FOR A WRIT OF CERTIORARI
OPINIONS BELOW
The opinion of the court of appeals (App., infra,
1a-38a) is reported at 809 F.3d 610. The opinion of
the district court (App., in#a, 39a-55a) is reported at
962 F. Supp. 2d 348. The prior opinion of the court of
appeals (App., infra, 56a-128a) is reported at 686
F.3d 1348.
JURISDICTION
The court of appeals entered its judgment on
November 10, 2015.
Petitioners Amphastar
Pharmaceuticals, Inc., International Medication
(1)
2
Systems, Ltd., Actavis, Inc., and Actavis
Pharmaceuticals, Inc. (collectively, "Amphastar")
timely filed a petition for rehearing en banc, which
was denied on February 17, 2016. This Court has
jurisdiction pursuant to 28 U.S.C. § 1254(1).
RELEVANT STATUTORY AND REGULATORY
PROVISIONS
The Hatch-Waxman safe harbor, 35 U.S.C.
§ 271(e)(1), provides in relevant part:
It shall not be an act of infringement to
make, use, offer to sell, or sell within the
United States or import into the United
States a patented invention *** solely for
uses reasonably related to the development
and submission of information under a
Federal law which regulates the
manufacture, use, or sale of drugs or
veterinary biological products.
INTRODUCTION
Petitioner Amphastar and Respondents
Momenta Pharmaceuticals, Inc. and Sandoz, Inc.
("Momenta") are competing generic manufacturers of
the unpatented drug enoxaparin. The FDA mandates
that manufacturers conduct testing to ensure the
bioequivalency (or sameness) of each batch of generic
enoxaparin with the brand-name drug (Lovenox), as
a condition of ongoing FDA approval, :in conformance
with the standard set forth in the United States
Pharmacopeia ("USP") compendium adopted by
Congress (21 U.S.C. § 351(b)). Amphastar uses the
sole USP-specified testing method to satisfy the
FDA’s requirement.
Momenta sued Amphastar for patent
infringement. Momenta alleged that Amphastar’s
Abbreviated New Drug Application ("ANDA")
approval was conditioned on Amphastar’s ongoing
use of the "official" USP-specified testing method and
that Momenta had patented that method. Reviewing
a preliminary injunction issued by the district court
against Amphastar, the Federal Circuit originally
held that Amphastar’s use of the USP-specified
method was protected under the Hatch-Waxman safe
harbor, which permits the use of a patented invention
"solely for uses reasonably related to the development
and submission of information under a Federal [drug]
law." 35 U.S.C. § 271(e)(1). The Federal Circuit
accordingly remanded with instructions to the
district court to consider whether the case was
"amenable to summary judgment of non-infringement
in favor of Amphastar." App., infra, 88a.
After the district court entered summary
judgment for Amphastar on remand, however, the
Federal Circuit reversed course: it held that the
same testing under the same authority was not
protected after all. The Federal Circuit based its
about-face on a purportedly new finding that
Amphastar’s testing was "routine," App., infra, 22a23a, a word nowhere found in the statute.
The Federal Circuit’s (second) decision cannot be
reconciled with this Court’s repeated admonitions
that the terms of the safe harbor must be interpreted
broadly to cover the "entire statutory scheme of
regulation." Eli Lilly & Co. v. Medtronic, Inc., 496
U.S. 661, 666 (1990). And the impermissible
narrowing of the safe harbor will create just the sort
4
of road blocks to lower-cost generic drugs that HatchWaxman was designed to avoid.
For that reason, as Momenta itself has
acknowledged at the preliminary-injunction stage of
this case, the scope of Section 271(e)(1) "is an issue of
exceptional, immediate importance to the
pharmaceutical industry." Petition for Certiorari at
28, Momenta Pharms., Inc. v. Amphastar Pharms.,
Inc., No. 12-1033 (filed Feb. 15, 2013) ("Momenta
Cert. Pet.") (capitalization omitted). Its significance
will only grow in light of the increasing prevalence of
complex biosimilar drugs, for which the FDA’s
bioequivalence-testing requirements are particularly
salient. Hijacking one of the required bioequivalence
tests, as Momenta has done, creates a roadmap for
blocking generic market entry in contravention of
Hatch-Waxman’s purposes. Given these stakes,
certiorari is warranted.
STATEMENT OF TI-IE CASE
A. Statutory and Regulatory Framework
To facilitate consumer access to lower-priced
drugs, Congress enacted special rules designed to
streamline generic drug approval in the Drug Price
Competition and Patent Term Restoration Act, Pub.
L. No. 98-417, 98 Stat. 1585 (1984), commonly known
as the Hatch-Waxman Act. See PLIVA, Inc. v.
Mensing, 131 S. Ct. 2567, 2574 (2011). Under the
Hatch-Waxman Act, "’generic drugs’ can gain FDA
approval simply by showing equivalence to a
reference listed drug that has already been approved
by the FDA." Id. at 2574 (citing 21 U.S.C.
§ 355(j)(2)(A)).
5
Among other reasons, because proving to the
FDA that a generic drug is bioequivalent to a namebrand drug can sometimes involve the use of a
patented invention, the Hatch-Waxman Act codified a
new exemption to the patent infringement statute-commonly referred to as the "safe harbor" provision.
The safe harbor provides:
It shall not be an act of infringement to
make, use, offer to sell, or sell within the
United States or import into the United
States a patented invention *** solely for
uses reasonably related to the development
and submission of information under a
Federal law which regulates
the
manufacture, use, or sale of drugs[.]
35 U.S.C. § 271(e)(1) (as amended).
The Federal Food, Drug, and Cosmetic Act, 21
U.S.C. § 301 et seq. ("FDCA" or "Act") is a "Federal
law which regulates the manufacture, use, or sale of
drugs," within the meaning of the safe-harbor
provision. Merck KGaA v. Integra Lifesciences I, Ltd.,
545 U.S. 193, 196 (2005) (citing 21 U.S.C. § 355(a)).
The safe harbor provides a "wide berth for the use of
patented [inventions] in activities related to the
federal regulatory process." Id. at 202. It covers both
pre-FDA-approval and post-FDA-approval activities.
App., infra, 18a.
B. Factual Background
1. This case involves a patent infringement
dispute between two competing manufacturers of
generic enoxaparin. Enoxaparin is a complex
molecule--derived from biological, rather than
6
chemical, sources--that treats and prevents lifethreatening blood clots. App., infra, 5a. Until 2010,
enoxaparin was available only as an expensive
brand-name drug called Lovenox. Id. Patents no
longer cover either enoxaparin or its manufacturing
process. 1
The FDA mandates that each new batch of
generic enoxaparin undergoes bioequivalence
testing--to show that it has the same composition as
Lovenox--as a running condition of FDA approval to
sell the drug. App., infra, 76a-77a. Demonstrating
generic enoxaparin’s bioequivalence to Lovenox,
however, poses a "potential problem" not present
with simpler drugs. Id. at 59a. "[U]nlike a typical
small molecule drug like penicillin, enoxaparin is
made up of a range of different molecules." Id.
Heparin, a pig-intestine product from which
enoxaparin is derived, contains "considerable
diversity" in its molecular structure. Id. at 58a. The
"obvious
complication"
with establishing
bioequivalence to Lovenox is that finished enoxaparin
is not made up of a single molecule but "a mixture of
a number of different low molecular weight heparin
molecules." Id. at 60a. Accordingly, the FDA
determined that it would allow generic
manufacturers to demonstrate bioequivalence or
1 In separate prior litigation, Sanofi-Aventis sued Amphastar
and Teva Pharmaceuticals USA, Inc. (another producer of
generic enoxaparin) for patent infringement as soon as they
filed their ANDAs. But Sanofi-Aventis’s patent was ultimately
held unenforceable, and the door was opened to generic
production of enoxaparin. See Aventis Pharma S.A. v.
Amphastar Pharms., Inc., 525 F.3d 1334, 1349 (Fed. Cir. 2008).
7
"sameness" through "five criteria, or ’standards for
identity,’ that together provide sufficient information
to conclude that generic enoxaparin has the ’same’
active ingredient as Lovenox." Id. at 60a-61a (some
internal quotation marks omitted).
One of those five standards for determining
sameness is at issue in this case: "[d]etecting the
presence of a 1,6 anhydro ring structure" at "the
reducing ends of between 15 percent and 25 percent
of its poly(oligo)saccharide chains." App., infra, 61a62a. The presence of that chemical structure in the
specified range indicates the drug’s bioequivalence to
Lovenox. Id. That requirement is now embodied in
the USP Monograph on Enoxaparin Sodium to which
all generic manufacturers, including Amphastar,
must conform. See id. at 84a-85a.
In addition, USP publishes an "official"
companion test--known as the General Chapter
<207> Test for 1,6-Anhydro Derivative for
Enoxaparin Sodium ("USP Method <207>")--for
establishing that a batch of enoxaparin meets the 1525% standard. App., infra, 86a. "Only those results
obtained by the methods and procedures given in the
compendium are conclusive.’’2
2 USP General Notices and Requirements § 6.30, available at
http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/USP3
4-NF29General%20Notices.pdf. Although the USP allows a
manufacturer to use an alternative to the official test if it
"provide[s] advantages in terms of accuracy, sensitivity,
precision, selectivity, or adaptability," any "[s]uch alternative
procedures and methods shall be validated" first in accordance
with USP procedures and also "must be shown to give
equivalent or better results." Id.
8
Because the FDCA prohibits the sale of drugs
that fail to meet the standard set forth in the
relevant USP Monograph, see 21 U.S.C. §§ 321(j),
331(a), 351(b), generic manufacturers must maintain
bioequivalence between enoxaparin and Lovenox on a
batch-by-batch basis as an ongoing "condition for
[FDA] approval and release." 21 C.F.R. § 211.165(d);
see id. § 211.165(a) ("For each batch of drug product,
there shall be appropriate laboratory determination
of satisfactory conformance to final specifications for
the drug product *** prior to release."). Any batch of
enoxaparin that is not successfully tested in
accordance with the "established specifications and
standards" in "the current revision of the [USP]," 21
C.F.R. § 211.194(a)(1)-(2), "shall be rejected" and its
approval for marketing withdrawn, id. § 211.165(f);
see 21 U.S.C. §§ 321(j), 331(a), 351(b). Manufacturers
like Amphastar are obligated to provide
documentation of their bioequivalence testing to the
FDA upon request. See 21 U.S.C. § 374(a)(4)(A)
("Any records or other information that the Secretary
may inspect under this section *** shall, upon the
request of the Secretary, be provided to the Secretary
*** in advance of or in lieu of an inspection[.]"); 21
C.F.R. § 211.180(c) (records "shall be readily
available for authorized inspection" by the FDA at
any time).
2. Amphastar was the first company to file an
ANDA with the FDA for generic enoxaparin. App.,
infra, 62a. In accordance with FDA requirements,
Amphastar tests samples of enoxaparin using the
"official" USP Method <207> to ensure
bioequivalence. Id. at 85a-86a. Indeed, before
approving the ANDA, the FDA "expressly require[d]"
9
Amphastar to conduct testing to prove conformance
with the USP standard. C.A. Supp. App. A15276A15277, No. 14-1276 (Fed. Cir. July 24, 2015) ("[T]he
above FDA documentation shows that Amphastar
was ’required’ by the FDA to test *** during and after
ANDA approval."); see also id. at A15368 (Mar. 22,
2007 FDA letter); Amphastar C.A. Supp. Br. 4, No.
14-1276 (Fed. Cir. Sept. 9, 2015). Amphastar would
not conduct such testing but for FDA’s demand. See
C.A. Supp. App. A15277 ("It is possible to make
enoxaparin and sell it without conducting [the
relevant] testing. *** Amphastar has no need to
conduct [such] testing other than to satisfy the FDA’s
requirement for such tests.").
Although Momenta was the third generic
manufacturer to file,3 the FDA approved Momenta’s
generic version of enoxaparin first. App., infra, 62a.
During the approximately one-year period it was the
lone supplier of generic enoxaparin on the market,
Momenta enjoyed profits on more than one billion
dollars in sales. Id.
Momenta is the assignee of U.S. Patent No.
7,575,886 ("the ’886 patent"), which claims "[a]
method for analyzing an enoxaparin sample." C.A.
App. 102; see also App., infra, 63a. Momenta alleges
that the ’886 patent covers USP Method <207>.
3 Momenta also sued another competitor, Teva
Pharmaceuticals (the second frier), for infringement. Teva is a
foreign manufacturer and therefore subject to liability only if its
enoxaparin is "made by a process patented in the United
States." 35 U.S.C. § 271(g). Because enoxaparin is not "made
by" Momenta’s patent, the Federal Circuit affirmed judgment
for Teva in Momenta’s infringement suit. App., infra, 16a.
10
App., infra, 86a. Despite USP’s policy of developing
publicly available standards and discouraging
adoption of patented tests,4 Momenta (a participant
in the relevant USP committee) never disclosed to
USP its then-pending patent application. The patent
ultimately issued after adoption of USP Method
<207> as the official companion test for the USP
Monograph.
C. Procedural History
1. Two days after Amphastar obtained FDA
approval to market its less-expensive version of
enoxaparin, Momenta sued Amphastar for allegedly
infringing Momenta’s ’886 patent. The premise of
Momenta’s complaint is that the ’886 patent covers
USP Method <207> and that, "in order for the FDA to
have approved Defendants’ manufacture of generic
enoxaparin," Amphastar must be performing that
bioequivalence test on each batch of enoxaparin. Am.
Compl. ¶ 27, C.A. App. 963. Momenta has repeatedly
acknowledged "[t]he FDA requires manufacturers of
generic enoxaparin" to perform the USP-specified
testing. Momenta C.A. Br. 41, No. 12-1062 (Fed. Cir.
Dec. 13, 2011); see Am. Compl. ¶¶ 22. 24, C.A. App.
962-963 ("FDA requires" testing); see also App., infra,
64a, 66a, 81a.
Crediting these allegations, the district court
granted Momenta a preliminary injunction that
4 See USP Guideline for Submitting Requests for Revision to
USP-NF: General Information for All Submissions (Apr. 2016),
available at http://www.usp.org/sites/defaultlfiles/usp_pdflEN/
USPNF/general-information-for-all-submissions.pdf.
11
categorically barred Amphastar from advertising,
offering for sale, or selling its enoxaparin. App.,
infra, 129a-161a.
2. In its first decision, the Federal Circuit
vacated the preliminary injunction. It held that
Amphastar’s USP-compliant bioequivalence testing,
which "generates information for submission
pursuant to the [FDCA]," "falls squarely within the
scope of the safe harbor" provision of the HatchWaxman Act, 35 U.S.C. § 271(e)(1). App., infra, 86a.
The Federal Circuit emphasized Momenta’s own
"allegations and concessions" that the allegedly
infringing activity was "necessary because the ’FDA
requires a generic manufacture[r]’" to undertake such
testing. Id. at 64a, 67a.
Focusing on the statutory text, the Federal
Circuit determined that Amphastar’s compliance
with the FDA mandate is "solely" for purposes
"reasonably related to *** [the] submission of
information" to the FDA, as the safe harbor requires,
for two reasons. 35 U.S.C. § 271(e)(1). First, the
testing is "reasonably related" to the development
and submission of information to the FDA, even if not
ultimately submitted, given the "requirement to
maintain records for FDA inspection." App., infra,
77a. Second, because "the information here is not
generated voluntarily by the manufacturer but is
generated by FDA requirements the manufacturer is
obligated under penalty of law to follow," the court
concluded, the information is "gathered solely for
submission to the FDA." Id. at 80a. The court of
appeals found that the testing at issue was "anything
but ’routine"’ because it implicated Amphastar’s very
ability to maintain its FDA approval and to continue
12
manufacturing and marketing its enoxaparin under
the ANDA. Id. The court rejected as inconsistent
with its precedent the dissent’s argument that
Amphastar’s testing was not "solely" for protected
activity because it also served a commercial end. Id.
at 84a (citing Abtox Inc. v. Exitro Corp., 122 F.3d
1019, 1030 (Fed. Cir. 1997)).
The Federal Circuit noted that its decision
applying the safe harbor to post-marketing-approval
testing was consistent with two decisions of this
Court. First, this Court’s decision in Eli Lilly & Co.
v. Medtronic, Inc., 496 U.S. 661, 666 (1990), held that
the safe harbor applies to the FDA’s "entire statutory
scheme of regulation." App., infra, 73a-74a
(emphasis omitted). Second, this Court’s decision in
Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S.
193, 202 (2005), held that "’It]here is simply no room
in the statute for excluding certain information from
the exemption on the basis of the phase of research in
which it is developed or the particular submission in
which it could be included.’" App., infra, 75a
(alteration in original) (emphasis omitted). In other
words, Section 271(e)(1) did not "create an exemption
applicable only to the research relevant to filing an
ANDA." Id. at 77a-78a (quoting Merck, 545 U.S. at
206). The Federal Circuit thus remanded for the
district court to consider entering "summary
judgment of non-infringement in favor of
Amphastar." Id. at 88a.
3. Momenta filed a petition for rehearing en
banc in the Federal Circuit and a petition for a writ
of certiorari to this Court, both of which were denied.
Order, No. 12-1062 (Fed. Cir. Nov. 20, 2012); Order,
No. 12-1033 (U.S. June 24, 2013).
13
4. On remand, applying the Federal Circuit’s
decision, the district court entered summary
judgment of non-infringement of the ’886 patent in
favor of Amphastar on the ground that Amphastar’s
testing "activities are *** protected by the safe
harbor" of 35 U.S.C. § 271(e)(1). App., infra, 7a.
5. Momenta filed an appeal, and--after
soliciting the views of the (non-party) Attorney
General on the interpretation of Section 271(e)(1)-the Federal Circuit reversed the district court as well
as its own prior decision.
The Federal Circuit first identified the purpose
of the safe-harbor provision as "facilitat[ing] market
entry upon patent expiration." App., infra, 17a
(quoting Classen Immunotherapies, Inc. v. Biogen
IDEC, 659 F.3d 1057, 1072 (Fed. Cir. 2011)). The
Federal Circuit highlighted a U.S. House of
Representatives Committee report statement
focusing on the need to permit "experimentation with
a patented drug product, when the purpose is to
prepare for commercial activity which will begin after
a valid patent expires." Id. at 17a-18a (quoting H.R.
REP. NO. 98-857(I), at 45 (1984), as reprinted in 1984
U.S.C.C.A.N. 2647, 2648) (emphasis omitted). The
Federal Circuit acknowledged that the safe harbor is
not restricted to pre-approval activities, but stated
that the safe harbor does not apply to information
"that may be routinely reported to the FDA, long
after marketing approval has been obtained." Id. at
19a (quoting Classen, 659 F.3d at 1070).
The Federal Circuit then turned to the question
whether "Amphastar’s submissions are appropriately
characterized as ’routine.’" App., infra, 21a. The
14
court held that they were because Amphastar tested
and developed information demonstrating
bioequivalence for "each batch" of enoxaparin. Id. at
22a. The court contrasted this testing with "nonroutine submissions that may occur both pre- and
post-approval," which are covered by the safe harbor.
Id. The court held that "routine quality control
testing of each batch" is not "reasonably related to
the development and submission of :information" to
the FDA. Id. at 22a-23a.
The Federal Circuit denied rehearing en banc.
App., infra, 162a-163a.
REASONS FOR GRANTING THE WRIT
The Court should grant review to correct once
again the Federal Circuit’s overly narrow
interpretation--cabined by its view of the legislative
history--of the Hatch-Waxman safe harbor, and to
construe instead the words Congress enacted. This
Court has examined the safe harbor twice since 1990;
each time it has rejected the Federal Circuit’s
attempts to impose atextual restrictions on the safe
harbor’s scope based on congressional "purpose"
supposedly revealed in legislative history. The
Federal Circuit nevertheless again eschewed the
statutory language in favor of a new restriction,
excluding so-called "routine" uses, that the court
made no attempt to locate in the safe harbor’s text-which, after all, is the best evidence of Congress’s
actual purpose.
Both sides agree that "the proper scope of the
safe harbor is a critical issue for the pharmaceutical
industry." Now that the Federal Circuit has
definitively resolved the scope of the safe harbor with
15
respect to FDA-mandated bioequivalence testing, it is
time for this Court to step in and give effect to the
terms that Congress wrote.
I.
THE FEDERAL CIRCUIT’S CATEGORICAL
EXCLUSION OF "ROUTINE" USES FROM
THE HATCH-WAXMAN SAFE HARBOR
CONFLICTS WITH THIS COURT’S
PRECEDENTS AND THE STATUTE
A.
Limiting The Safe Harbor’s Scope
Based On A General Purpose Divined
From Legislative History Conflicts
With Eli Lilly And Merck
1.
This Court’s precedents establish that
the safe harbor cannot be narrowed by
reference to legislative history
The safe harbor protects from infringement
certain acts so long as they are "solely for uses
reasonably related to the development and
submission of information under" the FDCA and its
implementing regulations. 35 U.S.C. § 271(e)(1).
Acknowledging the "breadth" of that language, this
Court has held "[t]here is simply no room in the
statute for excluding certain information from the
exemption on the basis of the phase of research in
which it is developed or the particular submission in
which it could be included." Merck, 545 U.S. at 202.
On two occasions, this Court has analyzed and
rejected judicially crafted restrictions in favor of the
safe harbor’s broad terms. First, in Eli Lilly, the
Court flatly rejected an attempt to qualify Section
271(e)(1)’s plain text based on limitations pulled from
the legislative history. 496 U.S. at 669. At issue in
16
Eli Lilly was whether the safe harbor--which
indisputably protects the use of patented inventions
in pursuit of new drug approval--also protects the
use of patented inventions in pursuit of medical
device approval. Id. at 665. This Court held that the
best reading of the relevant text ("a Federal law
which regulates the manufacture, use, or sale of
drugs") applies to the "entire statutory scheme of
regulation," not just to the drug-approval process. Id.
at 665, 666. Thus, even though the legislative history
"mentions only drugs," the Court refused to exclude
from the safe harbor’s unqualified and broad
language the use of patented inventions for the
purpose of obtaining approval of medical devices. See
id. at 669 & n.2. The actual terms of the safe harbor
apply to the FDCA’s "entire" statutory scheme--not
just to particular uses disclosed in the legislative
history. Id. at 666.
More recently, in Merck, this Court rejected
another judicially fashioned limitation on the safe
harbor’s scope. Relying on the Act’s ostensible goal of
protecting "clinical testing" on the road to new drug
approval, the Federal Circuit had determined that
certain research fell outside the safe harbor because
it was merely "general biomedical research to identify
new pharmaceutical compounds," rather than
"clinical testing to supply information to the FDA."
Integra Lifesciences I, Ltd. v. Merck KGaA, 331 F.3d
860, 866 (Fed. Cir. 2003).
In unanimously reversing, this Court held that
"It]hough the contours of [the safe harbor] provision
are not exact in every respect, the statutory text
makes clear that it provides a wide berth for the use
of patented drugs in activities related to the federal
17
regulatory process." Merck, 545 U.S. at 202. The
terms of the statute made "apparent" that "Section
271(e)(1)’s exemption from infringement extends to
all uses of patented inventions that are reasonably
related to the development and submission of any
information under the FDCA." Id. Congress neither
limited Section 271(e)(1)’s safe harbor "to the
development of information for inclusion in a
submission to the FDA; nor did it create an
exemption applicable only to the research relevant to
filing an ANDA for approval of a generic drug." Id. at
206.
"Rather," Congress "exempted from
infringement all uses of patented compounds
’reasonably related’ to the process of developing
information for submission under any federal law
regulating the manufacture, use, or distribution of
drugs." Id. (citing Eli Lilly, 496 U.S. at 674).
The upshot of these cases is clear: courts are to
respect the "wide berth" that Congress gave the users
of patented inventions "in activities related to the
federal regulatory process"; they are not to impose
artificial limitations grounded in the statute’s
perceived purposes drawn from statements in its
legislative history. Merck, 545 U.S. at 202. "There is
simply no room in the statute" to confine its
protections to particular types of submissions to the
FDA or the particular stage of the regulatory process.
Id.
2.
The Federal Circuit has engrafted an
atextual limitation on the safe harbor
in conflict with this Court’s cases
The Federal Circuit lost sight of the rules
articulated by this Court when it once again relied on
18
the safe harbor’s legislative history,, instead of its
text, to cabin its reach. Indeed, the Federal Circuit
could hardly have been more explicit about what it
was doing: it opened its analysis by noting that, as
the "legislative history makes *** clear," the
"purpose" of the statute was "to facilitate market
entry upon patent expiration." App., infra, 17a
(quoting Classen, 659 F.3d at 1072). :Relying on that
inquiry rather than the provision’s text, the Federal
Circuit held that the safe harbor could not protect
"information that may be routinely reported to the
FDA, long after marketing approval has been
obtained." Id. at 18a-19a (quoting Classen, 659 F.3d
at 1070). And because the court thought (incorrectly,
as explained infra) that Amphastar "makes no claim
that its accused, post-approval use of the patented
method is related to obtaining FDA approval," it
"conclude:d] [that] Amphastar’s submissions are
appropriately characterized as ’routine’"--and thus
that the safe harbor did not apply. Id. at 21a, 23a.
That analysis conflicts with this Court’s
precedents. The decision below relied on legislative
history in holding that the statute’s purpose is
limited to "obtaining FDA approval," App., infra, 23a,
without any "anchor~ in the text of the statute,"
Shannon v. United States, 512 U.S. 5’73, 583 (1994).
As discussed, Eli Lilly already rejected a similar
reliance on legislative history in the ,context of this
very safe harbor. See Eli Lilly, 496 U.S. at 669 n.2
("It is not the law that a statute can have no effects
which are not explicitly mentioned in its legislative
history.") (quoting Pittston Coal Group v. Sebben, 488
U.S. 105, 115 (1988)). In Merck, too, this Court
reversed a Federal Circuit opinion that had relied
19
extensively (and erroneously) on the legislative
history to narrow Section 271(e)(1)’s scope. See, e.g.,
Merck KGaA, 331 F.3d at 865 (relying on House
Committee report suggesting that safe harbor is
restricted to allowing "’a limited amount of testing so
that generic manufacturers can establish the
bioequivalency of a generic substitute"’), rev’d 545
U.S. 193.
The Federal Circuit has made the same mistake
again. Its focus on obtaining initial "FDA approval"
to the exclusion of other later submissions hearkens
back to the artificial distinction between pre- and
post-approval uses that was rightly rejected by the
Federal Circuit at the preliminary-injunction stage of
the case, and which even Momenta has since
condemned. See Momenta Cert. Pet. 4-5 (arguing
that earlier Federal Circuit decision erred in
"elevat[ing] legislative history *** over statutory
text") (citing Classen, 659 F.3d at 1071); see also U.S.
Amicus Br. at 20, GlaxoSmithKline v. Classen
Immunotherap~es, Inc., No. 11-1078 (U.S. Dec. 13,
2012) ( "U.S. Classen Br.") (similar). And that focus
ignores the fact that FDA requires the bioequivalence
testing at issue to first obtain and then to maintain
FDA approval. See p. 9, supra.
Indeed, the Federal Circuit’s scant analysis of
Section 271(e)(1) barely cites the text at all, and
exclusion of "routine"
nowhere locates the
submissions within it. There are ample textual
anchors for determiningthe safe harbor’s scope,
including the terms "solely," "reasonably related,"
and "submission." Indeed, the Federal Circuit took
the unusual step of seeking the Attorney General’s
views on "the meaning of the *** ’submission’ and
2O
’solely’ language." Order, No. 14-1276, at 2 (Fed. Cir.
May 7, 2015). Yet the Federal Circuit cast all of that
text aside, in favor of a word--"routine"--that is
nowhere to be found in the statute. It even went so
far as to quote dictionary definitions of that word, as
if that term were Congress’s rather than the Federal
Circuit’s own invention. App., infra, 21a (citing
definitions of the term "routine" from Webster’s and
the American Heritage Dictionary as meaning "of a
commonplace or repetitious character" and
"[h]abitual; regular") (alteration in original).~
But the safe harbor’s actual text--as distinct
from its perceived (or committee-reported)
"purpose"--in no way excludes supposedly "routine"
uses. On the contrary, Congress’s choice of the
phrase "related to"--particularly when preceded by
the term "reasonably"--is broadening language
meant to impart expansive, not restrictive, scope.
See Morales v. Trans World Airlines, Inc., 504 U.S.
374, 383 (1992) (The "ordinary meaning~’ of "relating
to .... is a broad one--’to stand in some relation; to
have bearing or concern; to pertain; refer; to bring
into association with or connection with.’") (quoting
Black’s Law Dictionary 1158 (5th ed. 1979)). That is
presumably why this Court has emphasized that the
safe harbor provides a "wide berth :for the use of
patented [inventions] in activities related to the
~ The word "routine" is drawn from vague dicta in the
Federal Circuit’s since-narrowed decision in Classen, 659 F.3d
at 1070--a decision that, as the Solicitor General told this
Court, "appeared seriously to misconstrue Section 271(e)(1)" by
adopting an atextual construction of the statute. U.S. Classen
Br. 20.
21
federal regulatory process," Merck, 545 U.S. at 202
(emphasis added)--not just, as the court of appeals
would have it, for experimentation in pursuit of
"obtaining FDA approval," App., infra, 23a. The
Federal Circuit’s elevation of legislative-historyderived purpose over text flatly contradicts the
teachings of Merck and Eli Lilly.
B.
The Federal Circuit Erred In Excluding
From The Safe Harbor Testing Required
For Ongoing FDA Approval
When the safe harbor’s text is examined, it
demonstrates the error in the Federal Circuit’s
decision. The safe harbor protects uses that are
"solely" for purposes "reasonably related" to the
"development and submission of information" to the
FDA. That language plainly encompasses FDAmandated post-approval testing (which is necessarily
designed to "developD *** information" for the FDA),
notwithstanding its habitual nature. At the same
time, it comfortably excludes ordinary manufacturing
methods (which generate such information only
incidentally, if at all).
Amphastar’s testing falls firmly on the protected
side of the line. Amphastar conducts the FDAmandated bioequivalence testing "solely" to
"develop D" the resulting information for "submission"
to FDA upon request, as the law requires--not as a
manufacturing quality-control step that it would
otherwise perform. App., infra, 79a-80a; see pp. 7-9,
supra. Indeed, Amphastar is accused of infringing a
patented "method for analyzing an enoxaparin
sample," C.A. App. 102 (emphasis added)--i.e., a
22
method for developing information for the FDA, not
for manufacturing.
Moreover, Amphastar uses the USP-specified
testing method only because the FDA specifically
required Amphastar (as a condition of ANDA
approval) to conduct 1,6-anhydro ring structure
batch-release testing to produce bioequivalence
information. See App., infra, 80a ("[T]he information
here is not generated voluntarily by the
manufacturer but is generated by FDA requirements
the manufacturer is obligated under penalty of law to
follow."); see pp. 7-9, supra. Conducting that testing
and documenting it for FDA submission was a
condition to receiving and maintaining FDA
approval--and thereby not only "reasonably related"
but directly related to safe-harbor protected uses.
The United States agreed that Amphastar
satisfies the "solely" and "submission" limitations,
because the testing records Amphastar generates
may be part of a "submission" to the FDA, U.S.
Amicus Br., No. 14-1276, at 15-16 (Fed. Cir. July 17,
2015), and because Amphastar makes "only a single
relevant ’use’" of the required testing method, id. at
23-24. It took the view, however, that Amphastar’s
commercial activity does not involve the
"development" of information and the testing is not
"reasonably related" to the submission of information
to the FDA. Id. at 2-3, 12.
The
latter conclusion fundamentally
misunderstands
how
the
FDA-specified
bioequivalence testing relates to
the safe harbor.
Amphastar "develops" new information through the
testing; it does not simply collect information that is
incidentally generated through the manufacturing
23
process. It performs the testing for the specific
purpose of creating the "information *** necessary
both to the continued approval of the ANDA and to
the ability to market the generic drug." App., infra,
79a. And the use of the USP-specified testing method
is not only "reasonably related" to developing
information to submit to the FDA; that is its raison
d’etre. Amphastar would not otherwise conduct such
testing. Amphastar’s testing therefore bears a
"substantial, proximate relationship" to developing
and submitting information to the FDA. U.S. Amicus
Br. at 18. At the very least, it is "reasonably related"
to that goal.
Under the Federal Circuit’s decision, however,
future applications of the safe harbor will not turn on
any of these factors--whether a particular activity is
"solely" for uses "reasonably related" to the
"development and submission" of information to the
FDA, as Section 271(e)(1) provides. Instead, the
Federal Circuit’s test turns on whether a particular
use can be considered "routine." Unsurprisingly, the
statute’s plain language better reflects Congress’s
balancing of "the need to stimulate innovation"
against the significant "public interest" in low-cost
generic drugs. App., infra, 69a (quoting H.R. REP.
NO. 98-857(II), at 30 (1984), as reprinted in 1984
U.S.C.C.A.N. 2686, 2714).
Even assuming an atextual "routine testing"
exception, the Federal Circuit erred when it reversed
its earlier conclusion that Amphastar’s FDA-required
testing is "anything but ’routine.’" App., infra, 80a.
That conclusion had nothing to do with how
"habitually" the tests were performed, id. at 22a, and
everything to do with the fact that "the information
24
here is not generated voluntarily by [Amphastar] but
is generated by FDA requirements the manufacturer
is obligated under penalty of law to follow," id. at
80a. After all, Momenta sued Amphastar based on
an allegation that Amphastar must have been using
the USP-specified testing method for FDA-required
bioequivalence testing on which continuing ANDA
approval was conditioned (and over which Momenta
claims a patent). Id. at 81a-82a. Testing required to
maintain ANDA authorization is not "routine"; it is
fundamental to the ability to secure ongoing approval
from the FDA. It therefore falls squarely within the
safe harbor’s protection of activities "reasonably
related to the development and submission of
information" to the FDA. 35 U.S.C. § 271(e)(1). The
Federal Circuit erred in concluding otherwise.
II.
WHETHER HATCH-WAXMAN PROTECTS
TESTING REQUIRED FOR CONTINUED
FDA APPROVAL IS AN EXCEPTIONALLY
IMPORTANT QUESTION
The Federal Circuit’s decision puts at risk the
ability of generic manufacturers to conduct FDArequired post-approval testing necessary to maintain
approval of an unpatented drug. Put another way,
the Federal Circuit’s decision may enable Momenta,
and other companies that seize on this strategy, to
monopolize the generic market for a drug~r, worse
yet, in the case of a brand-name manufacturer, to
extend its monopoly to block generic entry
altogether---even if (like here) the drug itself and
manufacturing process are unpatented. Allowing
competitors to sue for complying with FDA directives
to use particular bioequivalence or "sameness"
testing methods is not only perw~rse, but would
25
undermine the objectives of the Hatch-Waxman Act
and its safe harbor.
As Momenta has recognized, and as reinforced
by the Federal Circuit’s sua sponte call for the
Attorney General’s views, "It]he proper scope of the
safe harbor is a critical issue for the pharmaceutical
industry." Momenta Cert. Pet. at 28. The
application of the safe harbor to FDA-required
testing is of ever-growing importance given the
increasing prevalence of biologics, and hence
biosimilar generics, which require bioequivalence
testing on an ongoing basis as a condition first to
obtain and then to maintain FDA approval.6 Unlike
small-molecule drugs, and due to their complex
molecular characteristics, biologics "usually require
complex bioassays for batch release and stability
assessment.’’7 A neutered safe harbor could therefore
enable companies holding patents on FDA-approved
testing methods to stymie generic competition via
patent-infringement lawsuits--long after the patents
on the drug and its manufacturing method have
expired.
6 E.g., D. Meininger, IP Policy Forum: The Increasing
Importance of Biologics-Based Drugs in Pharmaceutical
Pipelines, 18 MARQ. INTELL. PROP. L. REV. 19, 20 (2014)
("biologics projected to comprise an ever greater component of
the biopharmaceutical product mix"), http:]]scholarship.law.
marquette.edu]cgi/viewcontent.cgi?article= 125 l&context=iplr.
7 Thomas Morrow & Linda Hull Felcone, Defining the
Difference: What Makes Biologics Unique, NIH BIOTECHNOLOGY
HEALTHCARE J. (Sept. 2004), at 24-26,
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564302/.
26
At stake, therefore, is whether the safe harbor
protects a generic manufacturer’s use of USPspecified bioequivalence testing methods to obtain
and maintain FDA approval, or instead whether
competitors can block market entry despite the lack
of any product or manufacturing patent. The Federal
Circuit chose the latter, thereby impeding HatchWaxman’s goal of "getting safe and effective generic
substitutes on the market as quickly as possible."
H.R. REP. No. 98-857(II), at 9, as reprinted in 1984
U.S.C.C.A.N. at 2686, 2693.
The Federal Circuit’s decision, including its
vague exclusion of "routine" uses from the safe
harbor, will have far-reaching consequences for the
pharmaceutical industry. Without a clear line that
protects generic manufacturers when they engage in
FDA-mandated testing, generic manufacturers will
be at perpetual risk of infringement liability, stifling
the marketing of competitively priced generic drugs
that Hatch-Waxman was designed to encourage.
This question of "exceptional, immediate importance"
to the industry, Momenta Cert. Pet. at 28, requires
the Court’s intervention.
27
CONCLUSION
The petition for a writ of certiorari should be
granted.
Respectfully submitted.
Pratik A. Shah
Counsel of Record
Anthony T. Pierce
James E. Tysse
Hyland Hunt
Emily C. Johnson
AKIN GUMP STRAUSS
HAUER & FELD LLP
Counsel for Petitioners
May 17, 2016